Measurement of phase-amplitude coupling (PAC) in slow oscillation and spindle events

Notes. (A) The origin of neural oscillations during sleep. SO slow oscillation; SP sleep spindle; SWR sharp wave ripple. In each subgraph, the vertical line indicates the typical amplitude of that sleep wave, while the horizontal line indicates the typical frequency and duration. Note that SPs also propagate along the cortex, and the figure only displays the origin. (B) Electrophysiology representation diagram of the SO-SP coupling. SO and SP amplitudes are normalized. The phase of SOs when SPs are at their maximum amplitude are recorded as the coupling phase. The occurrence of SPs and SO-SP coupling are not necessarily continuous as shown in the diagram. (C) Coupling preferred phase and strength diagram. (Left) The phase and strength used in the circular plot are simulated data from existing dataset for visualization purposes only. At the group level, the mean circular direction shows the preferred SO phase, while the mean vector length shows the strength of the precise coupling. (Right) The phase of SO peaks is noted as 0°, while the phase of SO troughs is noted as ±180°.

Hierarchical diagram of coupling measures

Notes. PETH peri-event time histogram; MVL mean vector length; MI modulation index. SPcSO Percentage of SPs coupled with SOs in all SP events. In contrast to the term “frequency” used throughout the text in reference to the neural oscillation, the coupling frequency in the diagram indicates the frequency of occurrence of SO-SP coupling events.

Risk of bias assessment summary plot adapted from ROBINS-I109

Notes. The most significant heterogeneity is revealed in the measurement of outcome, while the overall assessment indicated a moderate risk of bias across studies after requesting unreported results and data transformation. Based on the complexity of the type of measures involved in phase amplitude coupling analysis, we believe that this degree of risk of bias is acceptable. Specific evaluations for each study were reported in the Supplemental Material 3.

Forest and regression plots for the association between SO-SP coupling phase and memory retention.

Notes. (A) Overall model forest plot at study-level. Dashed lines indicate the 95% credible interval (CrI) of the pooled effect size. The black point and error bar for each study shows the adjusted estimation of effect size and 95% CrI combining data and prior information. The gray dots under each distribution show raw effect sizes of each study. Effect size-level plots can be found in Figure S5.1. (B) Meta regression plot with age as moderator. Blue lines represent 200 overplotted spaghetti fit lines to visualize predictions. (C) Moderator-level forest plot. Each box represents a type of moderator. Mixed Effect sizes with mixed conditions from different factor levels listed above. Weight Stacked weight of each moderation model in the paired model performance comparison between the moderator and overall (intercept-only) model. The stacked weight of the overall model in each pair of comparisons can be calculated as 1 - weight of the moderation model.

Result of directional hypothesis tests for each pair of factor levels (conditions) in overall and each moderation model of the coupling phase-memory association

Preferred slow oscillation-fast spindle coupling phase and its association with the memory retention

Notes. (A) Quadratic regression of the phase-memory association under different regions of PSG channels aggregated from studies included in the meta-analysis. 0° peak of SO upstate; ±π° trough of SO downstate; r circular-linear correlation coefficient; Zr standardized circular-linear correlation coefficient. Bars represent the mean memory retention scores per π/4 radian (45°). Dashed vertical line represents the mean preferred phase across studies. Colored quadratic fit line represents the direction of the relationship. The direction of their relationship gradually flips as the PSG channel moves from the front to the posterior area. Only under the frontal and central channels, fit lines display a quadratic relationship, with a peak of memory score near the up-state peak of SOs. In posterior channels, in contrast, the relationship is convex although it is not significant. Non-significant quadratic regression between SO-slow SP coupling and memory are reported in Supplemental Material 13. (B) Posterior distributions of mean preferred phases from the Bayesian circular mixed-effect model. The circular posterior distribution has been reported in the top-right corner, and the area between two black lines has been projected in a linear scale in the main graph. The vertical line reflects the up-state peak of slow oscillation. Dots and error bars reflect the mean and 95% credible intervals of phases detected from each channel cluster. Phase values have been reported as degrees. (C) Circular plot of the preferred coupling phase. Arranged from top to bottom in the order of frontal, central, and posterior. The direction of each colored dot represents the preferred coupling phase of each subject recorded from PSG channels in each cluster. The direction of the mean resultant vector indicates the mean preferred coupling phase across subjects, the width indicates the 95% credible interval of the mean coupling phase, while the length from 0 (center) to 1 (circumference) indicates the consistency of coupling phase across subjects.

Forest and regression plots for the association between SP amplitude and memory retention.

Notes. (A) Overall model forest plot at study-level. The solid vertical line represents the mean Pearson correlation coefficient under the null hypothesis. Dashed lines indicate the 95% credible interval (CrI) of the pooled effect size. The black point and error bar for each study shows the adjusted estimation of effect size and 95% CrI combining data and prior information. The gray dots under each distribution show raw effect sizes of each study. Effect size-level plots can be found in Figure S5.2. (B) Meta regression plot with age as moderator. Blue lines represent 200 overplotted spaghetti fit lines to visualize predictions. (C) Moderator-level forest plot. Each box represents a type of moderator. Mixed Effect sizes with mixed conditions from different factor levels listed above. Weight Stacked weight of each moderation model in the paired model performance comparison between the moderator and overall (intercept-only) model. The stacked weight of the overall model in each pair of comparisons can be calculated as 1 - weight of the moderation model.

Result of directional hypothesis tests for each pair of factor levels (conditions) in overall and each moderation model of the SP amplitude-memory association

Forest and regression plots for the association between coupling strength and memory retention.

Notes. (A) Overall model forest plot at study-level. The solid vertical line represents the mean Pearson correlation coefficient under the null hypothesis. Dashed lines indicate the 95% credible interval (CrI) of the pooled effect size. The black point and error bar for each study shows the adjusted estimation of effect size and 95% CrI combining data and prior information. The gray dots under each distribution show raw effect sizes of each study. Effect size-level plots can be found in Figure S5.3. (B) Meta regression plot with age as moderator. Blue lines represent 200 overplotted spaghetti fit lines to visualize predictions. (C) Moderator-level forest plot. Each box represents a type of moderator. Mixed Effect sizes with mixed conditions from different factor levels listed above. Weight Stacked weight of each moderation model in the paired model performance comparison between the moderator and overall (intercept-only) model. The stacked weight of the overall model in each pair of comparisons can be calculated as 1 - weight of the moderation model.

Result of directional hypothesis tests for each pair of factor levels (conditions) in overall and each moderation model of the coupling strength-memory association

Forest and regression plots for the association between coupling percentage and memory retention.

Notes. (A) Overall model forest plot at study-level. The solid vertical line represents the mean Pearson correlation coefficient under the null hypothesis. Dashed lines indicate the 95% credible interval (CrI) of the pooled effect size. The black point and error bar for each study shows the adjusted estimation of effect size and 95% CrI combining data and prior information. The gray dots under each distribution show raw effect sizes of each study. Effect size-level plots can be found in Figure S5.4. (B) Meta regression plot with age as moderator. Blue lines represent 200 overplotted spaghetti fit lines to visualize predictions. (C) Moderator-level forest plot. Each box represents a type of moderator. Mixed Effect sizes with mixed conditions from different factor levels listed above. Weight Stacked weight of each moderation model in the paired model performance comparison between the moderator and overall (intercept-only) model. The stacked weight of the overall model in each pair of comparisons can be calculated as 1 - weight of the moderation model.

Result of directional hypothesis tests for each pair of factor levels (conditions) in overall and each moderation model of the coupling percentage-memory association

Descriptive table of the meta-analysis result of measures of SO-SP coupling characteristics

Interpretation of the standardized circular-linear correlation coefficient

PRISMA flow diagram of literature search, screening, and inclusion for systematic review and meta-analysis

Summary of memory tasks

Interpretation of Bayes Factor (BF10) for the strength of evidence

Main characteristics for each study included in the meta analysis